We recently found a lysophospholipase D enzyme in rat brain that catalyzes the removal of ethanolamine and choline moieties from the alkyl ether and plasmalogen analogs of lysophosphatidylcholine and lysophosphatidylethanolamine. The enzyme requires Mg ions for activity and does not hydrolyze the substrates containing an acyl group attached at the 2-position of the glycerol. Since we reported the enzyme in brain, we have found that the liver also contains lysophospholipase D. This enzyme can function to redistribute ether moieties among lipid classes and it may be of great importance in their catabolism. The presence of phospholipase D-type activity was hitherto established only in plants. The goal of the proposed research is to characterize lysophospholipase D and to assess its role in the metabolism of lipids in different tissues and under different conditions including diseased states. Both the tissue distribution and the subcellular distribution of the enzyme will be determined. Lysosomes will be thoroughly examined for the presence of lysophospholipase D; activity there could explain how phosphodiesters derived from lipids are removed from the lysosomes. We hope to establish the exact specificity of lysophospholipase D by purifying the enzyme. Since the crude enzyme preparations contain acyl hydrolase activity, we have been unable to determine if the enzyme acts on the acyl analogs of the ether substrates; however, it is likely that it does. It is well known that lysophosphoglycerides are potent lysing agents and that they must not be allowed to build up in tissues. Lysophospholipase D may prove to be critically important for the removal of the ether-containing lysophosphoglycerides from tissues. Abnormalities in this function could play an important role in diseases, especially of tissues rich in other lipids -- cancer, nervous tissue, and the circulatory system. Lysophospholipase D levels in normal and diseased tissues will be examined to assess this possibility.